Placebo-controlled Trial of 5-hydroxytryptophan and Creatine for SSRI or SNRI Augmentation in Treatment Resistant Depression in Females

A Randomized, Double-blind, Placebo-controlled Trial of 5-hydroxytryptophan and Creatine for SSRI or SNRI Augmentation in Treatment Resistant Depression Associated With Hypobaric Hypoxia in Females

The investigators propose to determine if 8 weeks of dietary augmentation with oral 5g creatine monohydrate daily and 100 mg of 5-hydroxytryptophan (5-HTP) twice daily reduces hypoxia-related depressive symptoms measured by the 17-item Hamilton Depression Rating Scale (HAM-D) in women with SSRI- or SNRI-resistant depression, combined with the examination of changes in functional connectivity based on resting-state fMRI and changes in brain metabolism inferred from phosphorus-31 magnetic resonance spectroscopy.

Study Overview

• Status: Terminated
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: 5-hydroxytryptophan and Creatine; Other: Placebo control

Detailed Description

Serotonin and creatine are processed separately in the brain, and deficits in these brain biochemicals lead to distinct clinical problems. Therefore, investigators believe that treatment with a combination therapy, which could correct both deficits, would have a synergistic effect in the treatment of hypoxia-related depression and possibly other forms of treatment-resistant depression. Thus, investigators propose to investigate antidepressant efficacy of dietary 5-hydroxytryptophan (5-HTP) and creatine, as a means to restore the brain neurotransmitter and metabolic imbalances linked to chronic hypoxia caused by high altitude residence.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84054
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female gender, ages 25-40 years inclusive
• Current diagnosis of Major Depressive Disorder identified by the SCID-I
• Current HAM-D17 score of > 16
• Adequate adherence to any FDA approved SSRI or SNRI for at least 8 weeks
• Right-handed

Healthy Controls Inclusion criteria:

• Female gender, ages 25-40 inclusive
• No current or past DSM-5 diagnosis, as determined by clinical and structured interviews

Exclusion Criteria:

• Any non-MDD and non-anxiety psychiatric diagnosis, as identified by the SCID-I
• History of or current diagnosis of renal disease, such as chronic renal failure, acute renal failure or end stage renal disease
• Diabetes type I or II
• Current colitis or diverticulitis
• History of or current pulmonary disease
• History of cardiac disease or QTc > 500ms
• History of fibromyalgia, lupus, eosinophilia-myalgia syndrome, dermatomyositis, polymyositis, rheumatoid arthritis, psoriatic arthritis, mixed connective tissue disease, ankylosing spondylitis, or other related rheumatological condition
• History of or current seizure disorder
• Current serious suicide risk identified by the Columbia Severity Suicide Rating Scale
• Current treatment with an antipsychotic, mood stabilizer, or non-SSRI antidepressant
• Positive pregnancy test, pregnancy, failure to use adequate birth control method
• Previous diagnosis of serotonin syndrome or evidence of serotonin syndrome
• Use of any excluded drugs or medications including serotonergic drugs or medications (Table 2)
• Pre-existing eosinophilia (absolute eosinophil count > 500/uL)
• Contraindications to MRI: ferromagnetic implants, implanted devices, claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Depressed patients receiving study drug; Participants diagnosed with MDD	Drug: 5-hydroxytryptophan and Creatine
PLACEBO_COMPARATOR: Depressed patients receiving placebo; Participants diagnosed with MDD	Other: Placebo control
NO_INTERVENTION: Healthy Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hamilton Depression Rating Scale	The total Hamilton Depression (HAM-D) Rating Scale provides and indication of depression In general, the higher the total score the more severe the depression. HAM-D score level of depression: 10 - 13 mild; 14-17 mild to moderate; >17 moderate to severe. Range: 0 to 54	8 weeks

Collaborators and Investigators

• Sponsor: Brent Michael Kious, MD, PhD

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2016
• Primary Completion (ACTUAL): May 1, 2020
• Study Completion (ACTUAL): May 1, 2020

Study Registration Dates

• First Submitted: September 28, 2016
• First Submitted That Met QC Criteria: October 1, 2016
• First Posted (ESTIMATE): October 4, 2016

Study Record Updates

• Last Update Posted (ACTUAL): May 31, 2022
• Last Update Submitted That Met QC Criteria: May 26, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Psychotropic Drugs; Antidepressive Agents; Antidepressive Agents, Second-Generation; 5-Hydroxytryptophan
• Other Study ID Numbers: 94176

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED